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Single-cell mass-spectrometry quantifies the emergence of macrophage heterogeneity

View ORCID ProfileHarrison Specht, View ORCID ProfileEdward Emmott, Aleksandra A. Petelski, R. Gray Huffman, David H. Perlman, Marco Serra, Peter Kharchenko, Antonius Koller, View ORCID ProfileNikolai Slavov
doi: https://doi.org/10.1101/665307
Harrison Specht
1Department of Bioengineering and Barnett Institute, Northeastern University, Boston, MA 02115, USA
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Edward Emmott
1Department of Bioengineering and Barnett Institute, Northeastern University, Boston, MA 02115, USA
2Centre for Proteome Research, Department of Biochemistry, University of Liverpool, Liverpool, L69 7ZB, UK
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Aleksandra A. Petelski
1Department of Bioengineering and Barnett Institute, Northeastern University, Boston, MA 02115, USA
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R. Gray Huffman
1Department of Bioengineering and Barnett Institute, Northeastern University, Boston, MA 02115, USA
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David H. Perlman
1Department of Bioengineering and Barnett Institute, Northeastern University, Boston, MA 02115, USA
3Merck Exploratory Sciences Center, Merck Sharp & Dohme Corp., 320 Bent St. Cambridge, MA 02141
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Marco Serra
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
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Peter Kharchenko
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
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Antonius Koller
1Department of Bioengineering and Barnett Institute, Northeastern University, Boston, MA 02115, USA
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Nikolai Slavov
1Department of Bioengineering and Barnett Institute, Northeastern University, Boston, MA 02115, USA
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  • ORCID record for Nikolai Slavov
  • For correspondence: nslavov@alum.mit.edu
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Abstract

The fate and physiology of individual cells are controlled by protein interactions. Yet, our ability to quantitatively analyze proteins in single cells has remained limited. To overcome this barrier, we developed SCoPE2. It lowers cost and hands-on time by introducing automated and miniaturized sample preparation while substantially increasing quantitative accuracy. These advances enabled us to analyze the emergence of cellular heterogeneity as homogeneous monocytes differentiated into macrophage-like cells in the absence of polarizing cytokines. SCoPE2 quantified over 2,700 proteins in 1,018 single monocytes and macrophages in ten days of instrument time, and the quantified proteins allowed us to discern single cells by cell type. Furthermore, the data uncovered a continuous gradient of proteome states for the macrophage-like cells, suggesting that macrophage heterogeneity may emerge even in the absence of polarizing cytokines. Parallel measurements of transcripts by 10x Genomics scRNA-seq suggest that SCoPE2 samples 20-fold more copies per gene, thus supporting quantification with improved count statistics. Joint analysis of the data indicated that most genes had similar responses at the protein and RNA levels, though the responses of hundreds of genes differed. Our methodology lays the foundation for automated and quantitative single-cell analysis of proteins by mass-spectrometry.

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  • ∈ Data, code & protocols: scope2.slavovlab.net

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  • http://scope2.slavovlab.net

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 05, 2019.
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Single-cell mass-spectrometry quantifies the emergence of macrophage heterogeneity
Harrison Specht, Edward Emmott, Aleksandra A. Petelski, R. Gray Huffman, David H. Perlman, Marco Serra, Peter Kharchenko, Antonius Koller, Nikolai Slavov
bioRxiv 665307; doi: https://doi.org/10.1101/665307
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Single-cell mass-spectrometry quantifies the emergence of macrophage heterogeneity
Harrison Specht, Edward Emmott, Aleksandra A. Petelski, R. Gray Huffman, David H. Perlman, Marco Serra, Peter Kharchenko, Antonius Koller, Nikolai Slavov
bioRxiv 665307; doi: https://doi.org/10.1101/665307

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